Overexpression in MCF-7 Breast Cancer Cells Involved in the Proliferative Effects of Thioredoxin B Transactivation Is Increased But Is Not

Thioredoxin (Trx) is a small redox-active protein that provides reducing equivalents for key cysteine residues of proteins through thiol-disulfide exchange, such as the transcription factor nuclear factor-kB (NF-kB). NF-kB activation has been associated previously with cell growth and the inhibition of apoptosis. We have shown in earlier studies that overexpression of Trx in MCF-7 cells increases anchorageindependent growth. In this study, the activation of NF-kB was examined as a mechanism through which Trx overexpression might promote anchorage-independent growth. Constitutive NF-kB activity is elevated 4 –7-fold in Trx-overexpressing cells. NF-kB activity was inhibited in these cells by expressing a dominant-negative mutant of the IkBa protein (IkBaM). Expression of IkBaM in Trx-overexpressing cells dramatically reduced the Trx-associated increase in NF-kB activity but did not affect anchorage-dependent or -independent growth. The results suggest that increased growth in MCF-7 cells overexpressing Trx is not mediated by increased activation of the transcription factor, NF-kB. Additionally, activator protein-1 (AP-1), another transcription factor associated with growth, was increased up to 10-fold in Trxoverexpressing cells. Thus, AP-1 activation might contribute to the growth-promoting effect of Trx.